反应详情

温度

40 °C

2,3-Difluoro-5-iodobenzoic acid (3.0 g, 10.6 mmol) obtained in Step 1 was dissolved in toluene, thionyl chloride (3.0 ml, 41.1 mmol) and DMF (catalytic amount) were added, and the mixture was heated under reflux for 3 hr. The reaction mixture was concentrated under reduced pressure and THF (15 ml) was added to the residue to allow dissolution. The mixture was added dropwise to a solution of ethyl 3-dimethylaminoacrylate (1.66 g, 11.6 mmol) and triethylamine (1.77 ml, 12.7 mmol) in THF (10 ml) and the mixture was stirred with heating at 500C for 2.5 hr. After allowing to cool, the reaction mixture was filtered and washed with THF (10 ml). Aminoethanol (0.77 ml, 12.7 mmol) was added to the filtrate, and the mixture was stirred with heating at 40° C. for 1 hr. After allowing to cool, water was added to the reaction mixture and the mixture was extracted with ethyl acetate. The organic layer was washed with water and saturated brine, and dried over sodium sulfate. After filtration, the filtrate was concentrated under reduced pressure, and the obtained residue was purified by silica gel chromatography (ethyl acetate:hexane=2:1) to give the object product (3.8 g, yield 85%) as an E and Z mixed yellow solid.

1. temperaturethe mixture was heated
2. temperatureunder reflux for 3 hr
3. concentrationThe reaction mixture was concentrated under reduced pressure and THF (15 ml)
4. additionwas added to the residue
5. dissolutiondissolution
6. temperatureto cool
7. filtrationthe reaction mixture was filtered
8. washwashed with THF (10 ml)
9. stirringthe mixture was stirred
10. temperatureto cool
11. extractionthe mixture was extracted with ethyl acetate
12. washThe organic layer was washed with water and saturated brine
13. dry with materialdried over sodium sulfate
14. filtrationAfter filtration
15. concentrationthe filtrate was concentrated under reduced pressure
16. customthe obtained residue was purified by silica gel chromatography (ethyl acetate:hexane=2:1)